Perampanel for the control of glioma associated seizures – efficacy and safety

• Register: ANZCTR
• Last refreshed on: 15 November 2021
• Main ID: ACTRN12617000078358
• Date of registration: 13/01/2017
• Prospective Registration: Yes
• Primary sponsor: Melbourne Health
• Public title: Perampanel for the control of glioma associated seizures – efficacy and safety
• Scientific title: Perampanel for the control of glioma associated seizures – efficacy and safety: a pilot phase II randomised controlled trial
• Date of first enrolment: 17/07/2017
• Target sample size: 40
• Recruitment status: Stopped early
• URL: https://anzctr.org.au/ACTRN12617000078358.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Safety/efficacy;
• Phase: Phase 2

Countries of recruitment

Australia

Contacts

• Name: Dr Andrew neal

• Name: Dr Andrew Neal

Key inclusion & exclusion criteria

Inclusion criteria: Pre-operative phase (ie inclusion for 7T MRI)
1. 18 – 80 years
2. Radiological diagnosis of a supratentorial WHO grade II-III glioma
3. Planned surgical resection or biopsy of lesion
4. 3T MRI performed as clinical standard of care
5. Able to give informed consent
6. Experienced a pre-operative seizure attributed to glioma

Post-operative phase (ie inclusion for treatment intervention)
1. 18-80 years
2. Diagnosis of WHO grade II-III glioma
3. Less than 3 weeks from date of glioma resection or biopsy
4. Experienced a pre-operative seizure attributed to glioma
Exclusion criteria: 1. Previous non-tumour related neurosurgical procedures (excluding biopsy of glioma)
2. Pre-operative chemotherapy or radiotherapy
3. Receiving >1000mg daily of levetiracetam or multiple concurrent anti-epileptic drugs at time of randomization
4. Contraindication to 7T MRI
5. Significant risk factors for non-tumour associated epilepsy
- Previously diagnosed epilepsy (excluding benign childhood epilepsies)
- Additional epileptogenic intra-cranial pathology (including intra-cranial complications from glioma resection)
6. History of major psychiatric morbidity (such as psychiatric illness requiring hospitalisation or history of psychosis, major depression or suicidality) within the last 2 years
7. Pregnant or breast-feeding
8. Excessive alcohol or recreational drug use


Age minimum: 18 Years
Age maximum: 80 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Tumour associated epilepsy;Glioma;
Tumour associated epilepsy
Glioma

Neurological - Epilepsy

Cancer - Brain

Intervention(s)

The interventional drug to be utilized in this randomized controlled trial is the oral anti-epileptic drug, perampanel. Perampanel is an AMPA-receptor antagonist. Both intervention and comparator (levetiracetam) medications will be identically encapsulated.
Patients with WHO grade II-III supratentorial gliomas will be recruited pre-operatively and receive a 7T MRI scan. Post-operatively, patients will be randomized to receive perampanel or levetiracetam for 52 weeks.
Perampanel will be started at 2mg at night and over the first 4 weeks (escalation phase) will be uptitrated to by 2mg every 2 weeks. At the start of the assessment phase (week 5-52), perampanel will be increased to 6mg. Participants will remain on 6mg daily from week 5 until treatment completion at the end of week 52 unless seizures or side effects occur.

If post-operative seizures develop, perampanel can subsequently undergo 3 uptitrations of 2mg to a maximum of 12mg at night at the discretion of the investigator. If side effects develop and are intolerable, one dose reduction of 2mg can occur.

Participants will have 8 visits following randomisation over the 52-week study period, during which post-operative seizures, compliance and side effects will be assessment by investigators. Participants will be questioned regarding their medication adherence, and tablet/bottle counting will be performed to aid in compliance assessment. Visits will occur at 2, 4, 6, 8 weeks and 4, 6, 9, 12 months.

Primary Outcome(s)

Time to first seizure in assessment phase (weeks 5-52) - assessed by seizure diary[52 weeks from randomization]

Proportion of patients seizure-free for 24 or more continuous weeks in assessment phase (weeks 5-52) - assessed by seizure diary[52 weeks from randomization]

Secondary Outcome(s)

Seizure frequency during assessment phase (weeks 5-52).
Seizures per month (total seizures divided by 11) - assessed by seizure diary[52 weeks from randomization]

Proportion of patients who show improvement in anxiety symptoms (based on HADS score) from baseline to 52 weeks
Improvement defined as baseline score > 52 week score[52 weeks from randomization]

Overall survival - time from histological diagnosis to end of follow-up.[End of follow-up is 52 weeks after randomization, death or last follow-up if lost to follow-up]

Proportion of patients who continue on the allocated treatment at 52 weeks[52 weeks from randomization]

Proportion of patients who show improvement in anxiety symptoms (based on HADS score) from baseline to 16 weeks
Improvement defined as baseline score > 16 week score[16 weeks from randomization]

Proportion of patients who show improvement in QOL (Quality of Life) based on QOLIE-89 scores from baseline to 16 weeks by treatment group
Improvement defined as baseline score > 16 week score[16 weeks from randomization]

Frequency and type of adverse effects and serious adverse effects - assessed by LAEP questionnaire
Qualitative description of adverse effects which develop over the course of the trial[52 weeks from randomization]

Proportion of patients who show improvement in QOL (Quality of Life) based on QOLIE-89 scores from baseline to 52 weeks
Improvement defined as baseline score > 52 week score[52 weeks from randomization]

Secondary ID(s)

Nil known

Source(s) of Monetary Support

Royal Melbourne Hospital Neuroscience Foundation

Ethics review

Status: Approved
Approval date: 12/12/2016
Contact:

Melbourne Health Human Research Ethics Committee

Results

• Results available: Yes
• Date Posted: 05/11/2021
• Date Completed: 11/05/2020